The Effect of Serum Dilution on Free Thyroxine (T4) Concentration in the Low T4Syndrome of Nonthyroidal Illness

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Abstract
Progressive dilution of normal sera causes little change in free T4 concentrations. Similar dilution of sera containing drug inhibitors of T4 binding to serum proteins causes a progressive fall in free T4. The low T4 syndrome of nonthyroidal illness is thought to be associated with a circulating inhibitor(s) of T4 binding. It would be expected, therefore, that dilution of sera from the low T4 syndrome might also result in a fall in free T4 concentrations. We compared the effect of progressive serum dilution on free T4 concentrations in low T4 syndrome sera to those in normal, hyperthyroid, pregnancy, TBG-deficient and salicylate-containing sera. A tracer dialysis method proved inappropriate for studying dilution effects. Using a new dialysate RIA method to measure free T4, we found a progressive fall in free T4 concentrations in sera from patients with the low T4 syndrome similar to that in serum containing salicylate, but not to that in normal sera. The magnitude of the fall varied widely among individual patients. Free T4 methods which use a diluted serum sample will underestimate free T4 concentrations in the low T4 syndrome.